Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study.

To assess the efficacy and safety of tocilizumab (TCZ) plus methotrexate/placebo (MTX/PBO) over 2 years and the course of disease activity in patients who discontinued TCZ due to sustained remission. ACT-RAY was a double-blind 3-year trial. Patients with active rheumatoid arthritis despite MTX were randomised to add TCZ to ongoing MTX (add-on strategy) or switch to TCZ plus PBO (switch strategy). Using a treat-to-target approach, open-label conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), other than MTX, were added from week 24 if Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) >3.2. Between weeks 52 and 104, patients in sustained clinical remission (DAS28-ESR <2.6 at two consecutive visits 12 weeks apart) discontinued TCZ and were assessed every 4 weeks for 1 year. If sustained remission was maintained, added csDMARDs, then MTX/PBO, were discontinued. Of the 556 randomised patients, 76% completed year 2. Of patients entering year 2, 50.4% discontinued TCZ after achieving sustained remission and 5.9% achieved drug-free remission. Most patients who discontinued TCZ (84.0%) had a subsequent flare, but responded well to TCZ reintroduction. Despite many patients temporarily stopping TCZ, radiographic progression was minimal, with differences favouring add-on treatment. Rates of serious adverse events and serious infections per 100 patient-years were 12.2 and 4.4 in add-on and 15.0 and 3.7 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3×upper limit of normal were more frequent in add-on (14.3%) versus switch patients (5.4%). Treat-to-target strategies could be successfully implemented with TCZ to achieve sustained remission, after which TCZ was stopped. Biologic-free remission was maintained for about 3 months, but most patients eventually flared. TCZ restart led to rapid improvement. NCT00810199.

Huizinga TW ，Conaghan PG ，Martin-Mola E ，Schett G ，Amital H ，Xavier RM ，Troum O ，Aassi M ，Bernasconi C ，Dougados M ... -  《-》

Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY).

Dougados M ，Kissel K ，Sheeran T ，Tak PP ，Conaghan PG ，Mola EM ，Schett G ，Amital H ，Navarro-Sarabia F ，Hou A ，Bernasconi C ，Huizinga TW ... -  《-》

Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study.

Dougados M ，Kissel K ，Conaghan PG ，Mola EM ，Schett G ，Gerli R ，Hansen MS ，Amital H ，Xavier RM ，Troum O ，Bernasconi C ，Huizinga TW ... -  《-》

Tocilizumab discontinuation after attaining remission in patients with rheumatoid arthritis who were treated with tocilizumab alone or in combination with methotrexate: results from a prospective randomised controlled study (the second year of the SURPRIS

To evaluate the sustained remission and low disease activity after discontinuation of tocilizumab in patients with rheumatoid arthritis who were treated with tocilizumab alone or in combination with methotrexate. The SURPRISE study was a 2-year, open-label randomised controlled study. Among patients who had been randomised to additional tocilizumab (ADD-ON) or switch to tocilizumab (SWITCH) in the first year, those who achieved remission based on the disease activity score for 28 joints (DAS28-ESR<2.6) discontinued tocilizumab at week 52 and were observed for the following 52 weeks. The endpoint of the second year included tocilizumab-free remission and low disease-activity rates, functional outcome, radiological outcomes assessed with the modified total Sharp score (mTSS) and safety. The efficacy of reinstituted tocilizumab/methotrexate was also evaluated. A total of 105 patients who achieved remission at week 52 discontinued tocilizumab; 51 in ADD-ON continued methotrexate and 54 in SWITCH received no disease-modifying antirheumatic drugs. Sustained DAS28 low disease-activity rates were significantly higher in ADD-ON than in SWITCH (55%vs27%, p=0.005). Sustained remission rates at week 104 were 24% for ADD-ON and 14% for SWITCH (p=0.29). Radiological progression was comparable between both groups (mTSS; 0.37vs0.64, p=0.36). The restart of tocilizumab induced remission in all except two patients after 36 weeks, irrespective of concomitant methotrexate. Sustained low disease activity after tocilizumab discontinuation could be maintained with continued methotrexate in more than half of the patients. Retreatment with tocilizumab led to remission in more than 90% of patients. NCT01120366; Results.

Kaneko Y ，Kato M ，Tanaka Y ，Inoo M ，Kobayashi-Haraoka H ，Amano K ，Miyata M ，Murakawa Y ，Yasuoka H ，Hirata S ，Tanaka E ，Miyasaka N ，Yamanaka H ，Yamamoto K ，Takeuchi T ，SURPRISE study group ... -  《-》

Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from the randomised, placebo-controlled FUNCTION trial.

Investigate whether the efficacy and safety of intravenous tocilizumab (TCZ) demonstrated at week 52 in patients with early rheumatoid arthritis (RA) are maintained to week 104. Methotrexate (MTX)-naive patients with early progressive RA were randomly assigned to double-blind 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo or placebo+MTX for 104 weeks. Patients not receiving 8 mg/kg TCZ and not achieving Disease Activity Score-28 joints (DAS28-erythrocyte sedimentation rate (ESR)) ≤3.2 at week 52 switched to escape therapy (8 mg/kg TCZ+MTX). Analyses were exploratory. Intent-to-treat and safety populations included 1157 and 1153 patients, respectively. DAS28-ESR remission (<2.6) rates were maintained from weeks 52 to 104 (eg, 8 mg/kg TCZ+MTX, 49.3% to 47.6%). Placebo+MTX and 4 mg/kg TCZ+MTX escape patients' week 104 response rates were 51.4% and 30.5%, respectively. Inhibition of radiographic progression was maintained with 8 mg/kg TCZ (eg, 8 mg/kg TCZ+MTX mean (SD) change from baseline in modified total Sharp score: 0.13 (1.28), week 52; 0.19 (2.08), week 104). The safety profile of TCZ was consistent with that of previous reports. Patients with early RA treated with TCZ monotherapy or TCZ+MTX maintained clinical benefits during their second year of treatment with no new safety signals. NCT01007435; Results.

Burmester GR ，Rigby WF ，van Vollenhoven RF ，Kay J ，Rubbert-Roth A ，Blanco R ，Kadva A ，Dimonaco S ... -  《-》